Obesity is more than genes and food
(November 25th 2008) It seems that every other day scientists are coming up with new results that address the big question - just why do we get fat and then fatter? The latest answer:- Mothers to be must lose their own fat before getting pregnant. Melanie Estrella reports.
Obesity has been spreading epidemically around the globe. Aside from an unhealthy modern lifestyle, our genes seem to play a big role in determining our waistline. Some scientists, however, are now wondering how obesity has managed to spread through the population so fast. Instead of looking at genes, they have sought other explanations for a transmission of obesity. They have now found that obesity can be transferred maternally.
Several recent studies have revealed that the mother's bodyweight before and during pregnancy influences the future weight of her children. Heavy mothers are giving birth to persistently heavier children.
Rob Waterland, assistant professor of pediatrics at the USDA Children's Nutrition Research Center at Baylor College of Medicine, has demonstrated that epigenetic mechanisms affecting gene expression are involved in maternal transmission of bodyweight to offspring in mutant mice (International Journal of Obesity, 2008, July 15, Epub).
The scientists studied adiposity in three generations of mice carrying an altered version of the gene
agouti, which is normally involved in production of yellow pigment in hair follicles. If this gene is expressed in a mutated version, called Avy, throughout the whole body, the mice become covered in yellow dots and are prone to obesity if allowed open access to food.
These hungry mice were fed different diets:- One group received a regular diet, while the other was given food supplemented with folic acid, vitamin B12, betaine and choline. These added compounds enhance DNA methylation, resulting in silencing of genes - one of the mechanisms of epigenetic gene regulation.
While mice fed on a regular diet got fat, and fatter with each generation, mice fed on the DNA methylation-enhancing diet did not. This suggested that epigenetic processes are involved in the weight gain observed in the offspring of these fat mice. Perhaps epigenetic alteration, also termed epimutations, could provide one possible route for transmitting acquired features, like love handles, down the family line. While the details of this process are not yet known, Waterland and his colleagues think DNA methylation may be important in the development of the hypothalamus, the brain region that regulates appetite.
Waterland is not alone in suggesting that, during critical periods of development, nutrition and other environmental stimuli can perturb developmental pathways, thereby leading to permanent changes in gene expression, metabolism, and chronic disease susceptibility. He has coined the term "metabolic imprinting" to denote a subset of adaptive responses to early nutrition that are characterized by a susceptibility limited to a critical period of development that has a persistent effect lasting into adulthood.
The findings of Waterland's team agree with observations over the last decade by other scientists who have been discovering that environmental factors, such as diet or stress, can have far reaching affects that are transmitted to offspring without any detectable changes in the genomic DNA sequence. This so-called trans-generational epigenetic inheritance provides individuals with the ability to quickly adapt to modified conditions and transfer these features to their descendants. However, if not only the genes are being passed along to offspring, but also epigenetic features such as these, that can be modified by the environment, surely the current established theory of evolution needs revision?
Among the ideas that may need to be reconsidered lie those of the previously ridiculed Jean-Baptiste Lamarck who stated his own ideas on evolution fifty years before Charles Darwin. Lamarck believed in transmission of acquired features, including the famous case of giraffes stretching their necks. The emerging “New Lamarckism” now defines epigenetic alterations as inheritable units of environmentally acquired characteristics. It appears that Lamarck's theory may now be partially rehabilitated.
